Virion Therapeutics LLC

Highlights from the Data Presentation PHILADELPHIA, PA, USA I November 19, 2024 I Virion Therapeutics, LLC, a clinical-stage biotechnology company, developing novel T cell-based immunotherapies , today announced positive immunologic and continued safety and tolerability data, and anti-HBV immune responses, from the first-ever human study of its novel, first-in-class, checkpoint modifier immunotherapy, VRON-0200, for HBV functional cure, presented by Professor Grace Wong, M.D., from the Chinese University of Hong Kong, as a late breaker poster presentation at The Liver Meeting ® 2024 (The American Association for the Study of the Liver), in San Diego, California, US. These Phase 1b data, on the first 25 chronically infected hepatitis B patients, on nucleos(t)ide antiviral therapy, all of whom received a single, intramuscular (i.m.) injection of VRON-0200, demonstrated that it was safe and well-tolerated, with no significant adverse events reported and no clinically relevant abnormalities in laboratory assessments, including liver function tests. In 22 patients who had at least 28 days of immunologic follow up, a 5.5-fold increase in T cell responses was observed in 7 patients (32%), post-vaccination, with most maintaining responses above their baseline values out to day 91.  Additionally, four patients were observed to have HBV surface antigen (HBsAg) declines ranging from -0.4 to -2.3 log 10 IU/mL, after a single i.m. dose. Professor Wong commented: “Restoring immune function in chronically HBV-infected patients is needed in order to be able to discontinue HBV treatment and eliminate the infection. These results are highly promising for this chronically infected patient population, most of whom were infected at birth, in that a single VRON-0200 injection was able to both stimulate T cell responses, and lower HBsAg, in the blood, but also, that it is safe and well tolerated. The observed declines in HBsAg are of great interest given that VRON-0200 does not directly target HBsAg, and this suggests immune control of the virus in these patients. I look forward to seeing additional data, and longer follow up, from this study.” “These data highlight the potential of VRON-0200 as a simple, easy-to-administer, IFN-sparing immunotherapy, alone or in combination, for HBV functional cure,” said Dr. Sue Currie, COO of Virion, and one of the study authors. “VRON-0200 is the first new immunotherapy, other than monoclonal antibody checkpoint inhibitors and pegylated-interferon, to lower HBsAg without directly targeting it. As a result of these positive data, we are now investigating our first combination therapy with VRON-0200 with a cohort that includes elebsiran (siRNA) plus tobevibart (mAb), with the goal to potentially improve responses and bring a cure to the almost 300 million persons living with chronic HBV.  We look forward to sharing more results in early 2025.” Professor Ed Gane, M.D., from the University of Auckland, and one of the study authors, commented: “The non-immunologic/artificial removal of HBsAg (e.g., siRNA, small molecules), has not been shown to achieve durable off-treatment responses, and may not restore the needed immunity to control HBV infection. What makes these results so exciting is that a single VRON-0200 dose was able to produce HBsAg declines, showing evidence of anti-HBV immune control in these chronically infected patients.  These data, and the upcoming data from the now enrolling combination cohort, will inform future strategies for Functional Cure therapies.” Summary of VRON-0200 Phase 1b clinical trial design More details of the study can be found at ClinicalTrials.gov (Identifier: NCT06070051 ). About Chronic Hepatitis B Despite a preventative vaccine, cases of chronic hepatitis B (HBV) continue to rise, with an estimated 296 million persons infected worldwide and 820,000 deaths per year from HBV-related liver complications. Chronic HBV remains a global health issue with a high unmet medical need since there is no cure available. The current standard of care requires lifelong antiviral therapy to maintain control of the virus. About VRON-0200 VRON-0200 is a therapeutic immunotherapy, administered by intramuscular injection, designed with the goal of providing a functional cure for chronic HBV infection. While the virus itself stimulates HBV-specific CD8+ T cells, for those patients that can’t clear the initial infection, their T cells soon become exhausted, placing limits on their ability to proliferate and control the virus. Preclinical data support the hypothesis that VRON-0200, through checkpoint modification, can amplify, broaden, and enhance T cell responses that may include T cells that are not normally activated during a chronic HBV infection, which results in improved viral control. An ongoing Phase 1b trial has shown VRON-0200 to be safe, well tolerated, and immunogenic, in chronically HBV-infected patients on nucleos(t)ide therapy. About Virion Therapeutics (Virion) Virion Therapeutics, LLC is a clinical-stage company developing novel T cell-based immunotherapies to cure cancer and chronic infectious diseases that utilize proprietary genetically encoded checkpoint modifiers to enhance and broaden CD8+ T cell responses to a tumor or chronic infection. Founded in early 2018 to advance technology licensed from The Wistar Institute, an international leader in biomedical research, Virion has since developed a robust pipeline, including its lead VRON-0200 clinical program, and several additional IND-enabling programs, including its VRON-0300 oncology program for advanced solid tumors, leveraging its proprietary platform technologies. To learn more, visit www.VirionTx.com SOURCE: Virion Therapeutics

Highlights from the Data Presentation Ongoing safety (N=25) and immunogenicity (n=22), and first report of anti-HBV activity, presented in chronically HBV-infected patients following a single, prime-only intramuscular injection of VRON-0200 Over 4,952 patient safety days, VRON-0200 was well tolerated, with no serious adverse events (SAEs), study patient discontinuations, or laboratory abnormalities observed VRON-0200 induced CD8+ T cell responses in one third (7 of 22) of patients Responses were observed even in patients with limited pre-existing immunity A 5.5-fold increase in T cell responses at Day 28 was observed in the 7 responders Hepatitis B surface antigen declines ranging from -0.4 to -2.3 log10 IU/mL were observed, even though VRON-0200 does not directly target S-antigen, indicating anti-HBV immune activity PHILADELPHIA, Nov. 19, 2024 /PRNewswire/ -- Virion Therapeutics, LLC, a clinical-stage biotechnology company, developing novel T cell-based immunotherapies, today announced positive immunologic and continued safety and tolerability data, and anti-HBV immune responses, from the first-ever human study of its novel, first-in-class, checkpoint modifier immunotherapy, VRON-0200, for HBV functional cure, presented by Professor Grace Wong, M.D., from the Chinese University of Hong Kong, as a late breaker poster presentation at The Liver Meeting® 2024 (The American Association for the Study of the Liver), in San Diego, California, US. These Phase 1b data, on the first 25 chronically infected hepatitis B patients, on nucleos(t)ide antiviral therapy, all of whom received a single, intramuscular (i.m.) injection of VRON-0200, demonstrated that it was safe and well-tolerated, with no significant adverse events reported and no clinically relevant abnormalities in laboratory assessments, including liver function tests. In 22 patients who had at least 28 days of immunologic follow up, a 5.5-fold increase in T cell responses was observed in 7 patients (32%), post-vaccination, with most maintaining responses above their baseline values out to day 91. Additionally, four patients were observed to have HBV surface antigen (HBsAg) declines ranging from -0.4 to -2.3 log10 IU/mL, after a single i.m. dose. Professor Wong commented: "Restoring immune function in chronically HBV-infected patients is needed in order to be able to discontinue HBV treatment and eliminate the infection. These results are highly promising for this chronically infected patient population, most of whom were infected at birth, in that a single VRON-0200 injection was able to both stimulate T cell responses, and lower HBsAg, in the blood, but also, that it is safe and well tolerated. The observed declines in HBsAg are of great interest given that VRON-0200 does not directly target HBsAg, and this suggests immune control of the virus in these patients. I look forward to seeing additional data, and longer follow up, from this study." "These data highlight the potential of VRON-0200 as a simple, easy-to-administer, IFN-sparing immunotherapy, alone or in combination, for HBV functional cure," said Dr. Sue Currie, COO of Virion, and one of the study authors. "VRON-0200 is the first new immunotherapy, other than monoclonal antibody checkpoint inhibitors and pegylated-interferon, to lower HBsAg without directly targeting it. As a result of these positive data, we are now investigating our first combination therapy with VRON-0200 with a cohort that includes elebsiran (siRNA) plus tobevibart (mAb), with the goal to potentially improve responses and bring a cure to the almost 300 million persons living with chronic HBV. We look forward to sharing more results in early 2025." Professor Ed Gane, M.D., from the University of Auckland, and one of the study authors, commented: "The non-immunologic/artificial removal of HBsAg (e.g., siRNA, small molecules), has not been shown to achieve durable off-treatment responses, and may not restore the needed immunity to control HBV infection. What makes these results so exciting is that a single VRON-0200 dose was able to produce HBsAg declines, showing evidence of anti-HBV immune control in these chronically infected patients. These data, and the upcoming data from the now enrolling combination cohort, will inform future strategies for Functional Cure therapies." Summary of VRON-0200 Phase 1b clinical trial design VRON-0200 is a Phase 1b, multi-center, open-label, dose escalation, prime only, and prime plus boost, therapeutic immunotherapy study to evaluate the safety, tolerability, immunology, and other clinical measures: Inclusion criteria: Non-cirrhotic, HBeAg positive or negative, chronic hepatitis B patients currently taking nucleos(t)ide antiviral therapy with HBV DNA < 40 IU/mL and HBsAg < 500 IU/mL (< 1,000 IU/mL for Cohort 3) Dose escalation: Cohort 1 (low dose) (ENROLLED); Cohort 2 (high dose) (ENROLLED) Prime or Prime-Boost: In each cohort, patients are randomized to receive either a prime dose only or a prime and boost regimen Cohort 3: patients are randomized to receive VRON-0200 prime plus 6 monthly subcutaneous doses of elebsiran and tobevibart starting starting on Day 28, alone, or with a boost at Day 196 (ENROLLING) More details of the study can be found at ClinicalTrials.gov (Identifier: NCT06070051). About Chronic Hepatitis B Despite a preventative vaccine, cases of chronic hepatitis B (HBV) continue to rise, with an estimated 296 million persons infected worldwide and 820,000 deaths per year from HBV-related liver complications. Chronic HBV remains a global health issue with a high unmet medical need since there is no cure available. The current standard of care requires lifelong antiviral therapy to maintain control of the virus. About VRON-0200 VRON-0200 is a therapeutic immunotherapy, administered by intramuscular injection, designed with the goal of providing a functional cure for chronic HBV infection. While the virus itself stimulates HBV-specific CD8+ T cells, for those patients that can't clear the initial infection, their T cells soon become exhausted, placing limits on their ability to proliferate and control the virus. Preclinical data support the hypothesis that VRON-0200, through checkpoint modification, can amplify, broaden, and enhance T cell responses that may include T cells that are not normally activated during a chronic HBV infection, which results in improved viral control. An ongoing Phase 1b trial has shown VRON-0200 to be safe, well tolerated, and immunogenic, in chronically HBV-infected patients on nucleos(t)ide therapy. About Virion Therapeutics (Virion) Virion Therapeutics, LLC is a clinical-stage company developing novel T cell-based immunotherapies to cure cancer and chronic infectious diseases that utilize proprietary genetically encoded checkpoint modifiers to enhance and broaden CD8+ T cell responses to a tumor or chronic infection. Founded in early 2018 to advance technology licensed from The Wistar Institute, an international leader in biomedical research, Virion has since developed a robust pipeline, including its lead VRON-0200 clinical program, and several additional IND-enabling programs, including its VRON-0300 oncology program for advanced solid tumors, leveraging its proprietary platform technologies. To learn more, visit Contact: Virion Therapeutics, LLC, Dr. Sue Currie, Chief Operating Officer [email protected] SOURCE Virion Therapeutics, LLC WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

▎药明康德内容团队编辑 Precision BioSciences近日宣布，其主打在研体内基因编辑疗法PBGENE-HBV的临床试验申请（CTA）已获得摩尔多瓦（Moldova）的监管单位批准。PBGENE-HBV旨在通过消除乙型肝炎病毒（HBV）的共价闭合环状DNA（cccDNA），同时灭活整合在肝细胞中的HBV DNA，以达到功能性治愈慢性乙型肝炎的目的。该公司已启动1期临床项目，并准备进行患者给药。Precision公司预计向全球监管单位提交更多的CTA和IND申请。根据新闻稿，PBGENE-HBV是进入临床阶段的首个靶向HBV的体内基因编辑疗法。 据统计，在2019年全球约有3亿人患有慢性乙型肝炎感染。乙肝病毒可造成严重的肝脏感染并造成慢性疾病，约15%至40%的HBV感染患者可能会发展为肝硬化、肝衰竭或肝癌，这些并发症是导致HBV相关死亡的主要原因。乙肝病毒会在患者肝细胞内的细胞核中产生一种独特、游离的cccDNA，这是病毒进行复制时的模板，因此病患cccDNA的含量成为乙肝病患治疗与病情评估的一项重要指标。乙肝病毒DNA还能整合到细胞的DNA中，并成为生成乙肝表面抗原（HBsAg）的源泉之一。目前的肝治疗方式可以限制乙肝病毒的复制，但无法清除这些乙肝病毒的基因成分，这是导致病毒慢性感染与复发的原因，患者通常需要终身用药，这是乙肝治疗时的关键挑战。 PBGENE-HBV是一款基于Precision公司专有ARCUS基因编辑平台所开发的体内基因编辑疗法，设计专门靶向HBV的基因。该疗法通过脂质纳米颗粒将编码ARCUS核酸酶的mRNA递送至肝脏。当在HBV感染的肝细胞中表达时，ARCUS核酸酶可特异性切割乙型肝炎病毒DNA中高度保守的序列，旨在消除cccDNA并灭活整合到细胞DNA中的HBV基因。 ARCUS平台最初由北卡罗来纳州的科学家们于2006年创立公司时开发。与常见的CRISPR/Cas9技术不同，ARCUS使用的是一种源自藻类的编辑酶。根据新闻稿，PBGENE-HBV是首款进入临床阶段的靶向HBV慢性感染根本原因——cccDNA的疗法。 ▲ARCUS基因编辑平台介绍（图片来源：Precision BioSciences公司官网） 目前，“功能性治愈”是乙肝治疗的一大重点方向。这指的是虽然我们无法彻底将病毒清除出人体外，但通过治疗，可以将其限制在非常低的水平，低到在血液中都无法被检测出的地步。研究人员们也期望在如此低的水平之下，乙肝患者依靠自身的免疫力就能控制病情，而无需继续接受药物的治疗。除了Precision公司，同样正在开发靶向HBV基因编辑疗法的还有Excision BioTherapeutics。该公司旗下的EBT-107是一种基于CRISPR的双引导RNA（gRNA）基因疗法，旨在有效抑制病毒并消除持续感染的根本来源，该公司计划在2026年第一季度启动临床1b期研究。 浩博医药（AusperBio）旗下靶向所有乙肝病毒RNA的反义寡核苷酸（ASO）疗法AHB–137目前正在临床2期试验当中受检视。在临床前研究中，它可以激发所有乙肝病毒RNA的降解，并且显著降低HBsAg水平。Virion Therapeutics也正在开发潜在“first-in-class”检查点修饰免疫疗法VRON-0200，该疗法利用腺病毒载体，在抗原呈递细胞中表达HBV抗原的同时，还表达调节免疫检查点信号通路的重组蛋白，旨在提供慢性HBV感染患者的功能性治愈。今年6月公布该疗法的首个人体临床试验早期数据显示，在至少有28天免疫学随访的9名患者中，大多数患者在接种后显示出增强的T细胞反应。VTP-300则是一种由Vaccitech公司开发、与疫苗作用机制非常类似的免疫疗法。利用Vaccitech的黑猩猩腺病毒载体（ChAdOx1）和改良牛痘安卡拉病毒（MVA）载体表达乙肝病毒抗原，激发抗HBV的免疫应答，有望为慢性乙肝患者带来功能性治愈，目前该疗法正在临床2期试验当中接受评估。 参考资料： [1] Precision BioSciences Receives First Approval of Clinical Trial Application to Initiate PBGENE-HBV First-In-Human Study for the Treatment of Chronic Hepatitis B. Retrieved October 24, 2024 from https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-receives-first-approval-clinical-trial [2] Exclusive: Moldova clears first gene editing study for HBV in humans. Retrieved October 24, 2024 from https://endpts.com/exclusive-moldova-clears-first-gene-editing-study-for-hbv-in-humans/ [3] Pipeline. Retrieved October 24, 2024 from https://www.excision.bio/technology/pipeline 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。